The Natural History of Human Papillomavirus Related Condyloma In a Multinational Cohort of Men

Human papillomavirus (HPV) is the most common sexually transmitted infection in the United States, but few studies have examined the progression from HPV infection to disease in men. Genital condyloma are the most common clinical manifestation of HPV infection. Though not associated with mortality, condyloma are a source of emotional distress, and treatment is often painful with a high recurrence rate. The aims of this study were to examine the distribution of HPV types present on the surface of condyloma, estimate the incidence of condyloma overall and after type-specific HPV infections, assess the sociodemographic and sexual behavior factors independently associated with incident condyloma, and examine the concordance between HPV types detected on the surface and in the tissue of condyloma. Participants included 2,487 men from the United States, Brazil, and Mexico who were enrolled in the prospective HPV in Men (HIM) Study and followed every six months for up to four years. At each study visit men completed a computer-assisted-self-administered risk factor questionnaire and samples of healthy penile skin were obtained to test for HPV DNA. A trained clinician examined men for the presence of condyloma and swabbed the surface of lesions to test for HPV DNA. Men were followed for a median of 17.9 months and 112 incident condyloma were identified. Thirty-four external genital lesions were also biopsied to test for HPV within the lesion tissue. PCR was used to test for HPV DNA and Linear Array was used to genotype 13 oncogenic and 24 non-oncogenic HPV types in samples obtained from swabbing the lesion surface. The LiPa assay was used to genotype 20 HPV types in biopsy samples. The Kaplan-Meier method was used to estimate incidence and Cox proportional hazards models were used to examine factors independently associated with incident condyloma. Using biopsy samples as the gold standard, sensitivity and specificity were calculated to examine concordance between HPV types detected on the surface and within the tissue of condyloma. Condyloma incidence was 2.35 per 1,000 person-years. HPV 6 (43.8%), 11 (10.7%), and 16 (9.8%) were the most common types detected on condyloma. The probability of developing condyloma within 24-months of an incident HPV 6/11 infection was 14.6% (95% confidence interval (CI): 7.5-21.1). The median time to condyloma development was 17.1 months (95% CI: 12.4-19.3), with the shortest time to detection observed among men with incident HPV infections with types 6/11 only (6.2 months; 95% CI: 5.6-24.2). Factors associated with condyloma were incident HPV 6/11 infection (hazard ratio (HR)=12.42; 95% CI: 3.78-40.77), younger age (HR=0.43; 95% CI: 0.26-0.77; 45-70 vs. 18-30 years), high lifetime number of female partners (HR=5.69; 95% CI: 1.80-17.97); ≥ 21 vs. 0), and sexual behaviors in the previous three months including infrequent condom use (HR=2.44; 95% CI: 1.16-5.14; \u3c half the time vs. always), number of male sexual partners (HR=4.53; 95% CI: 1.68-12.20; ≥ 3 vs. none), frequent vaginal intercourse (HR=4.14; 95% CI: 1.32-13.01); ≥ 21 times vs. none), having a partner with condyloma (HR=2.38; 95% CI: 1.01-5.61), and being diagnosed with a sexually transmitted infection (HR=1.99; 95% CI: 1.17-3.39). HPV 6/11 plays an important role in condyloma development with the highest incidence and shortest time to condyloma development observed among men with incident HPV 6/11 infections. Recent sexual history was also strongly associated with incident condyloma in men, suggesting that prevention efforts targeting behavioral modification may be effective at reducing condyloma incidence among men who are not vaccinated. Samples obtained from the surface of condyloma lesions were both sensitive and specific as markers for the presence of any HPV, HPV6 and HPV11 in condyloma tissue, suggesting that sampling the surface of condyloma is a non-invasive and accurate marker of the HPV types present within the tissue